Audrey Riquet

Novel KCNQ2 and KCNQ3 Mutations in a Large Cohort of Families with Benign Neonatal Epilepsy: First Evidence for an Altered Channel Regulation by Syntaxin‐1A

Mutations in the KCNQ2 and KCNQ3 genes encoding for Kv7.2 (KCNQ2; Q2) and Kv7.3 (KCNQ3; Q3) voltage‐dependent K+ channel subunits, respectively, cause neonatal epilepsies with wide phenotypic heterogeneity. In addition to benign familial neonatal epilepsy (BFNE), KCNQ2 mutations have been recently found in families with one or more family members with a severe outcome, including drug‐resistant seizures with psychomotor retardation, electroencephalogram (EEG) suppression‐burst pattern (Ohtahara syndrome), and distinct neuroradiological features, a condition that was named “KCNQ2 encephalopathy.” In the present article, we describe clinical, genetic, and functional data from 17 patients/families whose electroclinical presentation was consistent with the diagnosis of BFNE. Sixteen different heterozygous mutations were found in KCNQ2, including 10 substitutions, three insertions/deletions and three large deletions. One substitution was found in KCNQ3. Most of these mutations were novel, except for four KCNQ2 substitutions that were shown to be recurrent. Electrophysiological studies in mammalian cells revealed that homomeric or heteromeric KCNQ2 and/or KCNQ3 channels carrying mutant subunits with newly found substitutions displayed reduced current densities. In addition, we describe, for the first time, that some mutations impair channel regulation by syntaxin‐1A, highlighting a novel pathogenetic mechanism for KCNQ2‐related epilepsies.

Usefulness of video-EEG monitoring in children

Video-EEG monitoring (v-EEG) was originally restricted to the evaluation for epilepsy surgery. It is now widely available and often utilized to clarify the nature of paroxysmal events or to identify the epileptic syndrome. It is important to define carefully the diagnostic value of this high-cost and time-consuming procedure. Few data on children are available. In this study, we have evaluated the utility of this procedure and the factors leading to a successful recording in children. We retrospectively reviewed 380 v-EEG done in 320 children. The rate of event detection was 59%. The v-EEG recorded a seizure in 40% (n=150), a non-epileptic event in 19% (n=73), and both seizure and non-epileptic events in 3% (n=11). Only 9% remained without diagnosis after v-EEG. The frequency of the usual events was the only factor contributing to a successful recording. This procedure confirmed the diagnosis of epilepsy in 43% of patients but excluded it in 25% of them. In children with epilepsy, the v-EEG allowed to define a new syndrome (30% of patients) or to improve clinical description and to identify the origin of the seizures (30%). The treatments were modified in 66% of patients following the v-EEG. Continuous video-EEG monitoring is an efficient and valuable procedure in the diagnosis and management of epilepsy and paroxysmal disorders in children.

Epileptic patients with de novo STXBP1 mutations: Key clinical features based on 24 cases.

Mutations in the syntaxin binding protein 1 gene (STXBP1) have been associated mostly with early onset epileptic encephalopathies (EOEEs) and Ohtahara syndrome, with a mutation detection rate of approximately 10%, depending on the criteria of selection of patients. The aim of this study was to retrospectively describe clinical and electroencephalography (EEG) features associated with STXBP1‐related epilepsies to orient molecular screening.

Levetiracetam-induced depression in a 5-year-old child with partial epilepsy

Depression in children and adolescents with epilepsy is common. Depression worsen quality of life in epilepsy patients. Neurobiological, social, and iatrogenic factors may play a role in depressive disorder development. We report a patient with partial epilepsy secondary to neonatal stroke, who developed depressive disorder as a result of levetiracetam (LEV) treatment. Our report illustrates the possible implication of iatrogenic factors in depression among epilepsy patients. However, recent data suggest that LEV may be effective in case of affective disorders. We discuss the factors linking epilepsy with depression. Because of its high incidence and its multiple physiopathologic factors, psychiatric comorbidity should be always assessed in pediatric epileptic patients.

Epilepsia partialis continua and defects in the mitochondrial respiratory chain

UNLABELLED Epilepsia partialis continua (EPC) is characterized by continuous myoclonic or clonic jerks repeated at short intervals followed by a slowly progressive neurological disorder. We report three patients with EPC and a defect in the mitochondrial respiratory chain. METHODS Clinical, neuroradiological, and biochemical data were reported. RESULTS The patients presented continuous myoclonic jerks at age of 8 months, 11 months and 6 years, respectively. Two of the three patients had a previous developmental delay. Neurological examination at first admission revealed extrapyramidal symptoms in all patients. Initial biological investigations suggested mitochondrial dysfunction. Initial EEG showed a continuous discharge of periodic spikes (0.5-1Hz). MRI studies were initially normal then progressed to cerebral hemiatrophia. EEG revealed both correlation and absence of correlation between spikes or sharp waves and myoclonic jerks. The activity of one or several complexes of the mitochondrial respiratory chain was reduced in the muscle samples of the three patients. No mutation of mtDNA was found. CONCLUSION Our report suggests that EPC can be due to mitochondrial respiratory chain disorders. Some clinical findings and initial investigations were indicative of a disorder of mitochondrial metabolism. Previous developmental delay, extrapyramidal symptoms and other organ involvement should suggest a possible mitochondrial etiology of EPC. In case of infant presenting EPC, mitochondrial respiratory chain disorder should be considered first.

Les antiépileptiques dans le traitement préventif de la migraine de l’enfant

According to the criteria of the International Headache Society, migraine occurs in approximately 5 to 10% of children. As many as 30% of young patients with migraine experience such frequent and disabling attacks, or have unsatisfactory results and/or experience adverse effects with pharmacologic treatment of acute migraine attack, that daily preventive medications are required. Many studies have investigated the use of antiepileptic drugs in this indication but there is a paucity of placebo-controlled studies. So far, in the setting of migraine with and without aura, only flunarizine and topiramate have proved their efficacy in more than one placebo-controlled study. Uncontrolled studies suggest the possible efficacy of valproic acid, gabapentin, levetiracetam, zonisamide, and magnesium in preventive therapy of childhood periodic syndromes. Most of antiepileptic drugs used in pediatric preventive therapy are well tolerated. The most common adverse events are asthenia and somnolence.

Epilepsy in young Tsc1+/− mice exhibits age‐dependent expression that mimics that of human tuberous sclerosis complex

To describe the epileptic phenotype of Tsc1+/− mice pups in comparison with age‐related seizures in human tuberous sclerosis complex (TSC).

Expanding the phenotype of SCA19/22: Parkinsonism, cognitive impairment and epilepsy

INTRODUCTION Spinocerebellar ataxia types 19 and 22 (SCA19/22) are rare conditions in which relatively isolated cerebellar involvement is frequently associated with cognitive impairment. Here, we report on new clinical features and provide details of the cognitive profile in two SCA19/22 families. METHODS Two families displaying an autosomal-dominant form of cerebellar ataxia underwent clinical examinations and genetic testing. RESULTS In addition to the classical clinical features of SCA, a wide spectrum of cognitive disorders (including visuospatial impairments) was observed. Eight patients had mild Parkinsonism, and five had epilepsy. Genetic testing showed that the KCND3 mutation (c.679_681delTTC, p.F227del) was present in both families. CONCLUSIONS Our findings broaden the phenotypic spectrum of SCA19/22, and suggest that KCND3 should be included in the list of candidate genes for epilepsy, Parkinsonism and cognitive impairment.